Mortality outcomes in 35,433 patients admitted for acute haemorrhagic stroke in Australia: A population-linkage study.

Background: Haemorrhagic stroke (HS) is an important cardiovascular cause of mortality worldwide. Trends in admission rates and outcomes, and predictors of outcomes, post-HS in Australia remain unclear. Methods: All New South Wales residents, Australia, hospitalized with HS from 2002 to 2017 were identified from the Admitted-Patient-Data-Collection database. Admission rates were adjusted to population size by sex, age-groups and calendar-year. Mortality was tracked from the death registry to 31-Dec-2018 and adjusted for admission calendar-year, age, gender, referral source, surgical evacuation following HS and comorbidities. Results: The cohort comprised 35,433 patients (51.1% males). Overall age-adjusted mean(±SD) admission rates were higher for males (63.6 ± 6.2 vs 49.9 ± 4.4 admissions-per-100,000-persons-per-annum). Annual admission rates declined for both sexes from 2002 to 2017 especially in those ≥60yo. In-hospital and 1-year mortality rates were higher for females than males (25.0% vs 20.0% and 40.6% vs 35.9% respectively, all p < 0.001). Adjusted in-hospital and 1-year mortality declined for men and women, overall decreasing by 45% (odds ratio 0.55, 95% confidence interval [CI] = 0.47-0.64), and 31% (hazard ratio 0.69,95%CI = 0.63-0.76) respectively between 2002 and 2017. Independent predictors of increased in-hospital and 1-year mortality included increasing age and Charlson comorbidity index, while male sex, a history of hyperlipidaemia and current smoking, and surgical evacuation following HS were associated with reduced mortality (all p < 0.001). Conclusion: HS incidence increases markedly with age. Although age-adjusted HS admission rates and post HS mortality have fallen, HS remains associated with high early and 1-year mortality, with females consistently associated with worse outcomes. Strategies to improve outcomes of these patients remain a clinical priority.

Outcomes Following Implantable Cardioverter-Defibrillator Insertion in Patients 80 Years of Age or Older: A Statewide Population Cohort Study.

BACKGROUND: Patients ≥ 80 years of age are underrepresented in major implantable cardioverter-defibrillator (ICD) trials, and real-world data are lacking. In this study, we sought to assess ICD utilisation, outcomes, and their predictors, in an unselected statewide population including patients ≥ 80 years old. METHODS: We extracted details of ICDs implanted from 2009 to 2018 in New South Wales (NSW), Australia from the Centre for Health Record Linkage administrative data sets. Analysis was stratified into age groups of < 60 years, 60-79 years, and ≥ 80 years. RESULTS: A total of 9304 patients (mean age 66.1 ± 13.1 years; 12.1% ≥ 80 years) had de novo ICD placement at an average rate of 1163 ± 122 patients per annum, with more implants in men in all age groups. After adjusting for NSW population size by sex, age group, and calendar year, mean implantation rates were 5.5 ± 0.6, 63.2 ± 8.6, and 52.7 ± 10.8 per 100,000 persons per annum in patients aged < 60 years, 60-79 years, and ≥ 80 years, respectively. In-hospital mortality was 0.4% and did not differ among age groups. However, 1-year mortality was 2.1%, 5.9%, and 10.7%, in those < 60 years, 60-79 years, and ≥ 80 years of age, respectively (P < 0.001), with hazard ratios for those aged ≥ 80 years of 4.3 (95% confidence interval [CI] 3.1-6.0) and those aged 60-79 years of 2.6 (95% CI 1.9-3.5) relative to those aged < 60 years (both P < 0.001) after adjusting for ICD indications, sex, implantation year, referral source, and comorbidities. In those aged ≥ 80 years, age > 83 years, congestive cardiac failure, chronic renal failure, neurodegenerative disease, and a higher Charlson comorbidity index score were each independent predictors of 1-year mortality. CONCLUSIONS: ICD use in patients aged ≥ 80 years and 60-79 years was 10-fold that in patients aged < 60 years, and perioperative outcomes were good in all ages, but there was substantially increased 1-year mortality in those aged ≥ 80 years. Careful selection based on age and comorbidity may further reduce 1-year mortality in patients ≥ 80 years old receiving ICDs.

Trends in Isolated Mitral Valve Repair or Replacement Surgery in Australia: A Statewide Cohort Linkage Study.

BACKGROUND: Global trends in mitral valve surgery (MVSx) suggest increasing repair compared with replacement, especially in the United States and European countries. The relative use, and outcomes of, MV repair and replacement in Australia are unknown. METHODS: New South Wales residents who underwent isolated MVSx between 2001 and 2017 were identified from the Admitted-Patient-Data-Collection database. Mortality outcomes were tracked to 31 Dec 2018 and adjusted based on age, sex, urgency of operation, and comorbidity status. RESULTS: The study cohort comprised 5,693 patients: 2020 (35%) underwent repair (MVr), 1,656 (29%) underwent mechanical replacement (mech.MVR), and 2017 (35%) underwent bioprosthetic replacement (bio.MVR). Respective median ages [interquartile range] were 67 yo [59-75 yo], 64 yo [55-71 yo], and 75 yo [68-80 yo] (p<0.001 across groups). Between 2001 and 2017, total MVSx increased steadily with population growth. Whereas the relative use of MVr remained static (34% to 38%), that for bio.MVR (22% to 50%) and mech.MVR (45% to 13%) changed significantly. MVr had the best outcome with 1.2% in-hospital, 2.5% 1-year, and 21.6% total cumulative mortality during a median follow-up of 6.5 years. Compared to MVr, the adjusted hazard ratio (aHR) for mech.MVR and bio.MVR for long-term mortality were 1.41 (95% confidence interval [CI]=1.24-1.61) and 1.73 (95% CI=1.53-1.95), respectively. Heart failure and sepsis were the main cardiovascular and noncardiovascular causes of death in all groups. CONCLUSION: In this statewide Australian cohort examined over 17 years, MVr is potentially underutilised despite having superior outcomes to MVR. Access to quality dataset which provides the indication for MVSx and quantitative clinical factors is critical to further improve MVr coverage and outcome MVSx.

Outcomes Following Triple Cardiac Valve Surgery Over 17-years: A Multicentre Population-Linkage Study.

INTRODUCTION: Studies have reported increasing triple valve surgery (TVS, defined as concomitant aortic, mitral and tricuspid valves surgery) incidence and improved postoperative survival. The epidemiology and outcome of TVS is not known in Australia. METHODS: From the Admission-Patient-Data-Collection registry, all New South Wales residents who underwent cardiac valve surgery between 1 July 2001 and 31 December 2018 were identified, with cause-specific mortality tracked from the death registry. RESULTS: Triple valve surgery comprised 1.2% (347/28,667 cases) of all valvular surgeries. Volumes rose from eight cases-per-annum in 2002 to a peak of 37 in 2012, and between 23 and 30 cases-per-annum since. Mean (±SD) age of study cohort (n=340 persons) was 68.2±15.2 years (50% male); 20.3% had concomitant coronary-artery-bypass-surgery (males vs females: 29.4% vs 11.2%, p<0.001). Main surgery on aortic and mitral valves was replacement (95.9% and 70.6% respectively). Tricuspid valve annuloplasty was performed in 90.6% of patients. Cumulative in-hospital, 180-day, and total mortality (mean follow-up=4.9±4.0 yrs) was 7.4%, 11.8% and 42.6%, respectively. Heart failure (24.0% in-hospital, 22.5% post-discharge) and sepsis (24.0% in-hospital, 20.0% post-discharge) were the main cause-specific deaths. There was no in-hospital stroke-related death. Age (median >72 yrs; hazard ratio [HR]=1.95, 95%CI=1.37-2.79), malignancy (HR=6.35, 95%CI=2.21-18.26), heart failure (HR=1.79, 95%CI=1.25-2.57) and chronic kidney disease (CKD) (HR=2.21, 95%CI=1.39-3.51) (all p<0.005) were independent predictors during intermediate-term follow-up. CONCLUSIONS: Triple valve surgery remains rare in Australia and is associated with high mortality. Multi-centred collaboration and access to comprehensive clinical data are required to identify the drivers of poor outcome.

Sex differences in rates of permanent pacemaker implantation and in-hospital complications: A statewide cohort study of over 7 million persons from 2009-2018.

BACKGROUND: Whether a bias exists in the implantation of permanent pacemakers (PPI) and complications according to sex and age in the Australian population is unclear. HYPOTHESIS: Population rate of PPI and its complications differed between men and women. METHODS: We examined the prevalence of PPI from January-2009 to December-2018 from datasets held by the New South Wales (NSW) Centre-for-Health-Record-Linkage, including patient's characteristics and in-hospital complications. All analysis was stratified by sex and age by decade. RESULTS: A total of 28,714 admissions involved PPI (40% women). The mean PPI rate (±standard-deviation) and median age (interquartile range) was 2,871±242 per-annum and 80yrs (73-86yrs), respectively. At the same time-period, the mean NSW population size was 7,487,393±315,505 persons (50% women; n = 3,773,756±334,912). The mean annual age-adjusted rate of PPI was 125.5±11.6 per-100,000-men, compared to 63.4±14.3 per-100,000-women (P<0.01). The mean annual rate of PPI increased from 2009-2017 by 0.9±3.3% in men, compared to 0.4±4.4% in women (P<0.01) suggesting a widening disparity. Total non-fatal in-hospital complications was higher in women compared to men (8.2% vs 6.6%, P<0.01), and this persisted throughout study period even after adjusting for multiple covariates. Overall, in-hospital mortality was low (0.73%) and similar between sexes. CONCLUSION: In a statewide Australian population exceeding 7 million, PPI rates were consistently nearly two-fold higher for men compared to women over 10-years, with an apparently widening disparity, that was not explained by age. Overall complication rates were higher in women. Future studies should examine the aetiology behind this disparity in PPI rates, as well as its complications.

A Pathway to Precision Medicine for Aboriginal Australians: A Study Protocol.

(1) Background: Genomic precision medicine (PM) utilises people's genomic data to inform the delivery of preventive and therapeutic health care. PM has not been well-established for use with people of Aboriginal and Torres Strait Islander ancestry due to the paucity of genomic data from these communities. We report the development of a new protocol using co-design methods to enhance the potential use of PM for Aboriginal Australians. (2) Methods: This iterative qualitative study consists of five main phases. Phase-I will ensure appropriate governance of the project and establishment of a Project Advisory Committee. Following an initial consultation with the Aboriginal community, Phase-II will invite community members to participate in co-design workshops. In Phase-III, the Chief Investigators will participate in co-design workshops and document generated ideas. The notes shall be analysed thematically in Phase-IV with Aboriginal community representatives, and the summary will be disseminated to the communities. In Phase-V, we will evaluate the co-design process and adapt our protocol for the use in partnership with other communities. (3) Discussion: This study protocol represents a crucial first step to ensure that PM research is relevant and acceptable to Aboriginal Australians. Without fair access to PM, the gap in health outcome between Aboriginal and non-Aboriginal Australians will continue to widen.

Outcomes of 16,436 patients requiring isolated aortic valve surgery: A statewide cohort study.

BACKGROUND: Aortic valve surgery (AVS) is the gold standard treatment for symptomatic aortic valve (AV) disease patients. We report the temporal trends in the incidence of patients requiring isolated AVS in an unselected statewide population and their mortality outcomes over 17-years. METHODS: Patients were identified from the New South Wales, Australia, Admitted-Patient-Data-Collection registry between 1-July-2001 and 31-December-2018. Annual case-volumes and survival outcomes, adjusted for age, sex, referral source, endocarditis, concomitant coronary-artery-bypass-grafting, comorbidities including atrial fibrillation, hypertension and Charlson comorbidity index, were compared across calendar years. RESULTS: The study cohort comprised 16436 patients who underwent isolated AVS (mean age: 72.2 ± 11.3y; 67.5% males). Annual case-volume increased from 768 to 1048 cases between 2002 and 2017 (r2 = 0.82; p < 0.0001). Surgical AV replacement (SAVR) with mechanical valves declined from 271 to 104 (r2 = 0.87; p < 0.0001) between 2002 and 2017. In contrast, bioprosthetic SAVR increased from 342 to 729 cases (r2 = 0.93; p < 0.0001). The 30-day, 6-month, and 1-year mortality rates improved progressively from 4.39%, 7.72%, and 9.19% in 2002, to 1.89%, 3.49%, and 4.68% by 2017. The adjusted odds ratio for 30-day mortality and hazard ratio for 1-year mortality were 0.33 (95% confidence interval [CI] 0.16-0.69, p < 0.01) and 0.09 (95% CI 0.07-0.12, p < 0.01), respectively. Similar improvements in outcomes were observed after implantation of mechanical or bioprosthetic aortic valves. Heart failure and sepsis were the most common cardiovascular-related and noncardiovascular-related causes death. CONCLUSION: The volume of AVS has increased progressively over time and has been associated with increased use of bioprosthetic valves and markedly improved 30-day and 1-year survival.

Everyday multitasking habits: University students seamlessly text and walk on a split-belt treadmill.

With increasing numbers of adults owning a cell phone, walking while texting has become common in daily life. Previous research has shown that walking is not entirely automated and when challenged with a secondary task, normal walking patterns are disrupted. This study investigated the effects of texting on the walking patterns of healthy young adults while walking on a split-belt treadmill. Following full adaptation to the split-belt treadmill, thirteen healthy adults (23±3years) walked on a tied-belt and split-belt treadmill, both with and without a simultaneous texting task. Inertial-based movement monitors recorded spatiotemporal components of gait and stability. Measures of spatial and temporal gait symmetry were calculated to compare gait patterns between treadmill (tied-belt and split-belt) and between texting (absent or present) conditions. Typing speed and accuracy were recorded to monitor texting performance. Similar to previous research, the split-belt treadmill caused an alteration to both spatial and temporal aspects of gait, but not to time spent in dual support or stability. However, all participants successfully maintained balance while walking and were able to perform the texting task with no significant change to accuracy or speed on either treadmill. From this paradigm it is evident that when university students are challenged to text while walking on either a tied-belt or split-belt treadmill, without any other distraction, their gait is minimally affected and they are able to maintain texting performance.

Gene methylation profiles as prognostic markers in ovarian clear cell and endometrioid adenocarcinomas.

Ovarian cancer is a cancer of high mortality. Aberrant gene methylation of tumor suppressor genes has been shown to be related to the development of malignancy. This study aimed to investigate the methylation of various genes in ovarian clear cell adenocarcinoma (OCCA) and ovarian endometrioid adenocarcinoma (OEA) and evaluate methylation biomarkers in terms of patient chemo-response and outcome. Eight candidate genes from 66 OCCA and 51 OEA patients were evaluated by methylation-specific polymerase chain reaction and capillary electrophoresis. Clinico-pathological parameters and patient outcomes were analyzed. The frequencies of gene methylation in RASSF1A (79% vs. 59%, p=0.025), E-cadherin (30% vs. 10%, p=0.011), and DLEC1 (71% vs. 43%, p=0.003) were higher in the patients with OCCA than in those with OEA. The chemo-resistant group had a significantly higher percentage of E-cadherin methylation (36.7% vs. 16.1%, p=0.036) than the chemo-sensitive group. In multivariate analysis (log-rank test), advanced stage (4.79 [2.10-10.94], p<0.001) was the only risk factor for mortality. Those with methylation of more than two out of three genes (E-cadherin, DLEC1, and SFRP5) had a shorter disease-free survival (1.89 [1.07-3.32], p=0.028) and overall survival (3.29 [1.57-6.87], p=0.002) than those with methylation of one or no gene. In advanced-stage malignancies, those with more than two out of the three gene methylations also had a shorter overall survival (3.86 [1.63-9.09], p=0.002) than those with methylation of only one or no gene. Patients with OCCA have different patterns of gene methylation than those with OEA. Methylation of the E-cadherin, DLEC1 and SFRP5 genes can be a prognostic biomarker for OCCA and OEA.